The long-term goal of this research is to understand the roles of of this research is to understand the roles of neuroendocrine homeostasis. CRF is the major integrator of these processes. Deviation of major integrator of these processes. Deviation of its regulation is its biological activity by binding two classes of proteins: CRF receptor activity by binding two classes of proteins: CRF receptor and CRF binding modulator. The objective of this proposal is to clarify the role of each objective of this proposal is to clarify the role of each CRF component mutations in each component of the CRF system. This involves: in each component of the CRF system. This involves: 1. Cloning of cDNAs encoding mouse CRF, CRF receptor A (CRF-RA), and CRF- 1. Cloning of cDNAs encoding mouse CRF, CRF receptor A (CRF-RA), and CRF- genomic clones containing these genes for targeted disruption of the CRF-RA of genomic clones containing these genes for targeted disruption of the studied. will be studied. 2. Investigation of effects of targeted disruption of CRF-RA and CRF-BP on 2. Investigation of effects of targeted disruption of CRF-RA and CRF-BP and stressful conditions including neuroendocrine, immune, and reproductive basal and stressful conditions including neuroendocrine immune and developing a strategy to generate mice with the components of CRF system developing a strategy to generate mice with the components of CRF system in the CRF system by intercrossing mice carrying mutations in different in the CRF system by intercrossing mice carrying mutations in different components of CRF system.